U.S. patent number 3,923,751 [Application Number 05/427,695] was granted by the patent office on 1975-12-02 for process for preparing polyamino acid in a non-polar solvent.
This patent grant is currently assigned to Ajinomoto Co., Inc.. Invention is credited to Yuji Iwashita, Mitsuru Sakuraba.
United States Patent |
3,923,751 |
Iwashita , et al. |
December 2, 1975 |
Process for preparing polyamino acid in a non-polar solvent
Abstract
Polyamino acids are prepared by an improved process by
polymerizing an amino acid halide salt such as an amino acid
chloride hydrochloride or an amino acid bromide hydrobromide in a
non-polar organic solvent which contains no active hydrogen atoms
in the absence of a base at elevated temperatures.
Inventors: |
Iwashita; Yuji (Kawasaki,
JA), Sakuraba; Mitsuru (Tokyo, JA) |
Assignee: |
Ajinomoto Co., Inc. (Tokyo,
JA)
|
Family
ID: |
26336683 |
Appl.
No.: |
05/427,695 |
Filed: |
December 26, 1973 |
Foreign Application Priority Data
|
|
|
|
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Dec 26, 1972 [JA] |
|
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48-3170 |
Aug 23, 1973 [JA] |
|
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48-94583 |
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Current U.S.
Class: |
528/328; 528/318;
528/315; 528/325 |
Current CPC
Class: |
C08G
69/08 (20130101); C08G 69/10 (20130101); D01F
6/68 (20130101) |
Current International
Class: |
D01F
6/58 (20060101); C08G 69/10 (20060101); C08G
69/08 (20060101); C08G 69/00 (20060101); D01F
6/68 (20060101); C08G 069/10 () |
Field of
Search: |
;260/78A |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
J Am. Chem. Soc. 76, 2814-2816, Frankel et al., (1954). .
J. of Organic Chemistry, Vol. 21, 1531-1532, Linschitz et al.,
(1956)..
|
Primary Examiner: Schain; Howard E.
Attorney, Agent or Firm: Oblon, Fisher, Spivak, McClelland
& Maier
Claims
What is claimed as new and intended to be covered by Letters Patent
is:
1. In a process for preparing a polyamino acid by polymerizing an
.alpha.-amino acid halide salt selected from the group consisting
of an .alpha.-amino acid chloride hydrochloride and an
.alpha.-amino acid bromide hydrobromide, the improvement which
comprises:
polymerizing said .alpha.-amino acid halide salt in a non-polar
organic solvent which contains no active hydrogen atoms in the
absence of a base at elevated temperatures such that said polyamino
acid is obtained having an intrinsic viscosity above 0.4.
2. The process of claim 1, wherein said non-polar organic solvent
has a dielectric constant below 4 at 20.degree.C.
3. The process of claim 2, wherein said non-polar organic solvent
is selected from the group consisting of hexane, heptane, octane,
benzene, toluene, xylene, carbon tetrachloride, trichloroethylene,
1,1,1-trichloroethane, tetrachloroethylene and mixtures
thereof.
4. The process of claim 1, wherein the reaction temperature ranges
from 40.degree.C to the boiling point of the non-polar organic
solvent.
5. The process of claim 1, wherein the polymerization reaction is
conducted under a pressure between 400 mm Hg and atmospheric
pressure.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to an improved process for preparing
polyamino acids from amino acid halide hydrohalides.
2. Description of the Prior Art
Polyamino acids which have a high degree of polymerization possess
excellent properties with respect to weather resistance, light
resistance, heat resistance, moisture permeability and feel or
texture. Also, the polyamino acids have been used as fibers, films,
coating materials for synthetic leather and for medical uses.
In general, polyamino acids have been prepared by polymerizing
amino acid-N-carboxy anhydrides which are derived from the reaction
between an amino acid and phosgene. However, despite the prior art
methods, it has been difficult to obtain polymers which are of a
high degree of polymerization.
Among the other prior art processes for preparing polyamino acids
without employing amino acid-N-carboxy anhydride, is the procedure
of polymerizing an amino acid chloride hydrochloride which is a
type of amino acid halide salt. Although this process has the
advantage that it is applicable in cases where N-carboxy anhydrides
cannot be obtained as with .beta.-amino acids, earlier attempts in
using this procedure have resulted in the formation of
oligopeptides having a low degree of polymerization.
Thus, this method is not particularly attractive. For example, M.
Frankel et al have attempted to polymerize amino acid chloride
hydrochlorides such as .alpha.-alanyl chloride hydrochloride,
.beta.-alanyl chloride hydrochloride, glycyl chloride hydrochloride
and leucyl chloride hydrochloride by heating the salts at
115.degree.-180.degree.C under a high vacuum in the absence of a
solvent or by dissolving the salt in a polar solvent such as
dimethylformamide which contains triethylamine and allowing it to
stand at room temperature for a long time. In either case however,
oligopeptides of the amino acids are only obtained which have a
polymerization degree of about 10 to 20 (J.Am.Chem.Soc., 76,
2814-2816 (1954).
A need, therefore continues to exist for a process by which amino
acids can be polymerized to give polymers having a high degree of
polymerization.
SUMMARY OF THE INVENTION
Accordingly, one object of the present invention is to provide a
method for polymerizing amino acids with a high degree of
polymerization.
Briefly, this object and other objects of the invention as
hereinafter will become more readily apparent can be attained by a
process of preparing a polyamino acid by polymerizing an amino acid
halide salt such as an amino acid chloride hydrochloride or an
amino acid bromide hydrobromide wherein the improvement comprises
polymerizing the amino acid halide salt in a non-polar solvent
which contains no active hydrogen atoms in the absence of a base at
elevated temperatures.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The term "polyamino acid having a high degree of polymerization" is
indicative of a polymer which has an intrinsic viscosity [.eta.]
above 0.4, when [.eta.] is measured at 30.degree.C in a
trifluoroacetic acid solution. Polyamino acids of this viscosity
may be shaped into fibers or films.
The formation of polyamino acids by polymerization of an amino acid
halide salt is an elimination reaction of hydrogen halide as shown
by the following equation. In view of the evolution of hydrogen
halide in the reaction, it would seem desirable to remove the
liberated hydrogen halide as quickly as possible from the reaction
system in order to obtain a polyamino acid having a high degree of
polymerization. ##SPC1##
Of course, in the reaction above, R is an organic radical and X is
chlorine or bromine.
When the hydrogen halide which is evolved in the above reaction is
quickly removed from the reaction medium by means of high vacuum or
by neutralization with an organic base in an organic solvent as is
practiced in the prior art procedures, the type of reaction which
tends to predominate is the initiation of the polymerization
reaction rather than the steady growth of added amino acid monomers
to form a polymer chain. Consequently, the preference for the
formation of oligomers of the amino acids which have a low degree
of polymerization or the formation of diketopiperazine derivatives
(a dimer of the amino acid) predominates. Furthermore, when the
reaction is conducted in a polar solvent such as dimethylformamide,
the evolved hydrogen halide dissolves in the solvent, and acts as
polymerization inhibitor thus preventing the formation of polymers
having a high degree of polymerization.
In the process of the present invention the evolved hydrogen halide
does not dissolve in a non-polar solvent, and hence the
polymerization reaction proceeds smoothly. Also, since no base
exists in the reaction system, the compulsory removal of the
hydrogen halide from solution does not occur. Thus, the type of
reaction which promotes the initiation of the polymerization of the
amino acid does not predominate or is minimized. Thus, polyamino
acids can be formed which have a high degree of polymerization.
Also, very little polymerization of the amino acid occurs when the
amino acid is heated in a polar solvent in the absence of base.
Even if some polymerization occurs under these conditions, only
oligopeptides having a low degree of polymerization are
obtained.
Thus, the use of a non-polar organic solvent as a reaction medium
and the absence of base in the reaction medium are important
conditions which promote the formation of polyamino acids having a
high degree of polymerization by heating amino acid halide salts in
an organic solvent.
The amino acid halide salts which may be employed as monomers in
the present invention can be readily prepared, for example, by
reacting an amino acid with phosphorus pentachloride or phosphorus
pentabromide. Suitable amino acids include .alpha.-amino acids,
.beta.-amino acids, .omega.-amino acids and .alpha.-alkylamino
acids. However, neutral amino acids such as glycine, alanine,
.beta.-alanine, valine, leucine, isoleucine, methionine,
.alpha.-aminobutyric acid, phenylalanine, serine, threonine; acidic
amino acids such as glutamic acid and aspartic acid; acidic amino
acid-.omega.-esters such as .gamma.-methyl glutamate, .gamma.-ethyl
glutamate and .beta.- methyl aspartate; basic amino acids such as
lysine and ornithine; N-derivatives of basic amino acids such as
N.sup..omega.-benzoyllysine, N.sup..delta.-carbobenzoxyornithine;
and O-derivatives of amino acids containing hydroxy groups such as
O-benzylserine are especially preferred amino acids. The amino
acids used can be optically active, racemic mixtures or mixtures
thereof.
The amino acid halide salts can be employed singly or in mixtures
thereof. Therefore, homopolymers or copolymers of the amino acids
can be formed.
Non-polar solvents which are suitable as reaction media in the
present process are those which do not possess an active hydrogen
atom and which are inert to the amino acid halide salt monomers.
Especially preferable non-polar solvents include those which have a
dielectric constant below 4 at 20.degree.C. Suitable solvents
include aliphatic hydrocarbons such as hexane, heptane and octane;
aromatic hydrocarbons such as benzene, toluene and xylene;
aliphatic chlorinated hydrocarbons such as carbon tetrachloride,
trichloroethylene, 1,1,1-trichloroethane, tetrachloroethylene and
mixtures of these solvents. The non-polar solvents may also be
employed without difficulty in admixture with polar solvents which
do not possess active hydrogen atoms provided that the dielectric
constant values of the solvent mixture is maintained below 4. By
carefully selecting those solvents which are capable of dissolving
the polymers produced which, of course is a function of the amino
acid halide salt employed, the polymerization reaction can be
optimized to yield polymers which have a high degree of
polymerization. Similarly good results can also be obtained when
the particular solvent chosen only partially dissolves the polymer.
Usually it is desirable to use a solvent in which the concentration
of polymer formed is above 0.05% by weight at ordinary
temperatures.
In conducting the process of the present invention, an amino acid
halide salt is dissolved or suspended in a non-polar solvent in a
ratio of 0.5 - 50 ml of solvent per gram of amino acid halide salt.
The mixture is heated at a temperature of from 40.degree.C to the
boiling point of the solvent employed. The preferred temperature is
in the range of 50.degree.C to 120.degree.C. The polymerization
reaction can be conducted at ordinary atmospheric pressures.
However, somewhat reduced pressures of from 400 mm Hg up to
atmospheric pressure can also be used in order to remove some of
the generated hydrogen halide gas from the reaction system, if
desired. The reaction time is not critical and can be varied
depending on the reaction temperature employed. Normally, however,
a time period of 4 hours to about 24 hours is suitable.
After completion of the polymerization reaction, if the polymer is
totally soluble in the reaction medium, the polymer solution may be
directly used as a "dope" for forming fibers or films. If desired,
however, the polymer can be separated from solution by the addition
of suitable non-solvents to the solution such as methanol, acetone
and petroleum ether after removal of the solvent according to the
demand.
Having generally described this invention, a further understanding
can be obtained by reference to certain specific examples which are
provided herein for purposes of illustration only and are not
intended to be limiting unless otherwise specified.
EXAMPLE 1
Two gram quantities of L-leucyl chloride hydrochloride were heated
at 65.degree.C for 24 hours in 20 ml of various solvents. Each
reaction mixture was added to 50 ml of methanol to precipitate the
polymer which was separated by filtration and dried. The results
obtained are summarized in Table 1.
TABLE 1
__________________________________________________________________________
Run Polymer No. Solvent yield (%) [.eta.]*
__________________________________________________________________________
1 Heptane 97.9 1.53 2 Carbon tetrachloride 98.1 2.83 3
Trichloroethylene 100.0 1.10 4 Tetrachloroethylene 98.6 1.80 Fiber
and film-forming 5 Methylchloroform 87.6 0.81 ability 6 Benzene
99.4 1.10 7 Toluene 99.2 1.72 The present invention 8 Ethylacetate
41.0 0.10 9 Acetonitrile 51.6 0.10 No fiber or film- Control 10
Dimethylformamide ** -- forming ability
__________________________________________________________________________
*indicates that the viscosity values were measured at 30.degree.C
in trifluoroacetic acid. **indicates that the product is soluble in
methanol and a polymer does no form.
As is apparent from the data in Table 1, polyamino acids having a
high degree of polymerization can be obtained which are capable of
forming fibers and films only by the use of non-polar solvents as a
reaction medium.
REFERENCE EXAMPLE
Two grams of L-leucyl chloride hydrochloride were added to 20 ml of
a solution of 1.95 g of triethylamine in toluene and were allowed
to stand at room temperature for 48 hours. The reaction solution
was concentrated to dryness under reduced pressure, and 50 ml of
water was added to the residue to dissolve the triethylamine
hydrochloride and to precipitate a polymer which was filtered and
dried.
The yield of polymer was 28.0%. A sample of the polymer was
dissolved in trifluoroacetic acid, and the intrinsic viscosity
[.eta.] was measured at 30.degree.C and was found to be 0.10. The
polymer was obtained as a powder and no films could be formed from
the polymer. A similar experiment was conducted at 60.degree.C and
very much the same results were obtained. Similarly, the polymer
obtained could not be cast into a film.
EXAMPLE 2
A 20 gram amount of L-phenylalanyl chloride hydrochloride was added
to 80 ml of toluene and was heated at 70.degree.C for 18 hours. The
reaction mixture was poured into 500 ml of methanol and the
precipitated polyphenylalanine was filtered and dried. The yield of
product was 98.8%. A sample of this polymer was dissolved in
trifluoroacetic acid and [.eta.] was measured at 30.degree.C and
was found to be 0.98.
A 10 gram amount of the polymer was dissolved in a mixed solvent
consisting of 130 ml of chloroform and 10 ml benzene. The resultant
solution was spread over a glass plate with an applicator having a
slit width of 0.5 mm. The coated plate was dried at 80.degree.C for
20 minutes. The film which was removed from the casting surface had
a thickness of 18.mu., a tensile strength of 4.83 kg/mm.sup.2, an
elongation of 14% and a favorable touch.
EXAMPLE 3
A 40 gram amount of DL-leucyl chloride hydrochloride was added to
400 ml of tetrachloroethylene and was heated at 100.degree.C for 8
hours with stirring while the reaction system was maintained under
a reduced pressure of 600 mm Hg with the aid of an aspirator. The
reaction mixture was added to 800 ml of methanol to precipitate
polyleucine which was filtered and dried. A sample of this polymer
was dissolved in trifluoroacetic acid and [.eta.] was measured at
30.degree.C and was found to be 1.50.
A 20 gram amount of the polymer was dissolved in a mixed solvent of
200 g of chloroform and 6 g or formic acid, and a small amount of
insoluble material was removed by filtration. The resultant polymer
solution was extruded by a quantitative pump through a nozzle
containing 20 spinnerets of 0.08 mm diameter into a
methylethylketone coagulation bath. The fiber obtained was
stretched 1.5 times. This fiber had a tensile strength of 3.2
g/denier and an elongation of 20.2% and had excellent touch and
luster.
EXAMPLE 4
A 2 gram quantity of DL-alanyl chloride hydrochloride was heated at
70.degree.C for 24 hours in 20 ml of carbon tetrachloride. The
precipitated polyalanine in the reaction mixture was filtered and
dried. The yield of polymer was 84.3%. A sample of this polymer was
dissolved in trifluoroacetic acid and [.eta.] was measured at
30.degree.C and was found to be 0.48.
EXAMPLE 5
A 2 gram amount of L-.alpha.-aminobutyryl chloride hydrochloride
was heated at 70.degree.C for 18 hours in 20 ml of a mixed solvent
of trichloroethylene and ethyl acetate (mixture ratio = 8/2). The
reaction mixture was poured into 50 ml of methanol to precipitate
poly-.alpha.-aminobutyric acid which was filtered and dried. The
yield of polymer was 85.6%. This polymer had a viscosity value
[.eta.] of 0.63 at 30.degree.C in trifluoroacetic acid.
EXAMPLE 6
A 10 gram amount of .gamma.-methyl glutamyl bromide hydrobromide
was heated at 100.degree.C for 10 hours in 100 ml of octane. The
reaction mixture was poured into 200 ml of methanol to precipitate
poly-.gamma.-methyl glutamate which was filtered and dried. The
yield of polymer was 79.4%. This polymer had a viscosity value
[.eta.] of 0.72 at 30.degree.C in trifluoroacetic acid.
EXAMPLE 7
A 3.0 g amount of L-leucyl chloride hydrochloride was suspended in
30 ml of octane in a three-necked flask, and the stirred mixture
was heated at the reflux temperature under atmospheric pressure.
The heating was continued for 7 hours at the end of which no
evolution of hydrogen chloride gas was observed. The reaction
mixture was concentrated under reduced pressure to remove octane,
and the residue was washed with methanol and then water and dried.
By this procedure was obtained 1.7 g of resinous polyleucine which
had a viscosity value [.eta.] of 1.8 at 30.degree.C in
trifluoroacetic acid. This polymer was dissolved in hot benzene and
concentrated to about a 5% solution. The solution was spread over a
glass plate which was dried to remove solvent whereby a transparent
film was obtained.
EXAMPLE 8
A 1.5 gram amount of L-phenylalanyl chloride hydrochloride and 1.35
g of L-leucyl chloride hydrochloride were suspended in 30 ml of
heptane in a three-necked flask. The stirred suspension was heated
at the reflux temperature for 10 hours under atmospheric
pressure.
After removal of the heptane from the reaction mixture by
concentration, the resultant residue was washed with methanol and
then with water and dried. By this procedure was obtained 1.1 g of
a copolymer of phenylalanine and leucine. This copolymer had a
viscosity value [.eta.] of 1.0 at 30.degree.C in trifluoroacetic
acid. A good film was obtained when it was cast from its solution
which was composed of a mixed solvent of chloroform and benzene.
The film had a thickness of 25.mu., a tensile strength of 3.52
kg/mm.sup.2 and an elongation of 25%.
EXAMPLE 9
A 10 gram amount of L-phenylalanyl chloride hydrochloride was
suspended in 100 ml of octane in a three-necked flask and then
heated at reflux for 8 hours. The reaction mixture was treated in
the same manner as described in Example 7 to obtain 6.5 g of
polyphenylalanine having a viscosity value [.eta.] of 0.69 at
30.degree.C in trifluoroacetic acid.
The polymer was dissolved in chloroform and the resulting solution
was cast on a glass plate. The film which was removed from the
casting surface had a thickness of 22.mu., a tensile strength of
3.91 kg/mm.sup.2, an elongation of 15% and good feel.
EXAMPLE 10
A 5 gram amount of DL-leucyl chloride hydrochloride was suspended
in 100 ml of n-octane and heated under reflux for 4 hours. The
reaction mixture was concentrated to dryness under reduced
pressure, and the residue was boiled with 100 ml of water and then
refluxed with 100 ml of ethanol for 1 hour to remove unreacted acid
chloride hydrochloride and a polymer which had a low degree of
polymerization. The yield of polyleucine was 3 g ( [.eta.] = 0.6 at
30.degree.C in trifluoroacetic acid). The polymer was dissolved in
tetrachloroethylene and the resulting solution was spread over a
glass plate with an applicator having a slit width of 0.7 mm and
dried. The film which was removed from the casting surface had a
thickness of 15.mu., a tensile strength of 2.86 kg/mm.sup.2, an
elongation of 20% and good touch.
EXAMPLE 11
A 4.3 gram amount of DL-leucyl chloride hydrochloride was suspended
in 50 ml of n-heptane and was heated under reflux for 8 hours. The
reaction mixture was treated in the same manner as described in
Example 7, whereby 2.5 g of polyleucine having a viscosity value
[.eta.] of 0.72 at 30.degree.C in trifluoroacetic acid was
obtained.
EXAMPLE 12
A mixture of 6.3 g of L-valinyl chloride hydrochloride and 6.7 g of
L-leucyl chloride hydrochloride was heated under reflux in 100 ml
of n-octane. The reaction mixture was treated in the same manner as
described in Example 7 whereby 7.4 g of L-valine-L-leucine
copolymer having a viscosity value [.eta.] of 0.50 at 30.degree.C
in trifluoroacetic acid was obtained.
The polymer was soluble in benzene and gave a film which had a
thickness of 15.mu., a tensile strength of 2.65 kg/mm.sup.2 and an
elongation of 23%.
Having now fully described this invention, it will be apparent to
one of ordinary skill in the art that many changes and
modifications can be made thereto without departing from the spirit
or scope of the invention as set forth herein.
* * * * *